THERAPEUTIC EFFECTS OF LOXIGLUMIDE, A CHOLECYSTOKININ ANTAGONIST, ON CHRONIC CONSTIPATION IN ELDERLY PATIENTS - A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, CONTROLLED TRIAL

Severe chronic constipation is a common health problem, particularly a mong elderly nursing-home patients. Cholecystokinin (CCK) is involved in the regulation of colonic motility, and the blockade of CCK(A) rece ptors with loxiglumide, a potent and highly specific CCK(A) antagonist , dramatically accelerates colonic transit time in healthy human volun teers. The effect of loxiglumide on the bowel habits and colonic trans it time in 21 chronically constipated nursing-home patients (mean age 83, range 71-89 years) was studied in a randomized, placebo-controlled , double-blind cross-over study. Loxiglumide 800 mg t.i.d. or identica l-looking placebo tablets were given orally in sequence with a 7-day w ashout period in between for 21 days each. The number of spontaneous b owel movements and that of administered enemas was recorded for each 3 -week phase. At the end of each treatment period colonic transit time was assessed using radio-opaque markers. Treatment with loxiglumide si gnificantly (P < 0.005) accelerated colonic transit time from 113 +/- 6 to 81 +/- 10 h. The frequency of weekly bowel movements increased fr om 3.9 +/- 0.5 (placebo) to 4.9 +/- 0.5 (loxiglumide) (P < 0.006), whi le the number of enemas over the 3 weeks decreased from 2.7 +/- 0.6 to 1.3 +/- 0.4 for placebo and loxiglumide, respectively (P < 0.005). No serious side-effects were observed and there were no signs of exocrin e pancreatic insufficiency induced by loxiglumide. The blockade of CCK (A) receptors with loxiglumide significantly improves chronic constipa tion in geriatric patients. Loxiglumide may therefore constitute the p rototype of a new class of potent therapeutic agents effective in the treatment of constipation.